Male sexual function after laparoscopic total mesorectal excision.

AIM: The aim of this prospective study was to clarify the frequency of male sexual dysfunction after laparoscopic total mesorectal excision (LTME) and to examine the relationship between pelvic autonomic nerve (PAN) preservation status and functional outcomes. METHOD: Candidates for LTME were included in this study. PAN preservation status after LTME was examined in detail by video review. Patients completed a functional questionnaire (the International Index of Erectile Function) before and 3, 6 and 12 months after the operation. RESULTS: Twenty-six patients who underwent LTME were assessable. Detailed video reviews identified inadvertent PAN damage during surgery. PAN injury was observed in 11 cases (41%), including eight cases (32%) of inadvertent PAN damage (incomplete preservation group). There was a trend toward increasing inadvertent PAN injury rate in patients with high body mass index and large tumours. The results from all patients who underwent LTME showed no deterioration in total International Index of Erectile Function or its domain scores 12 months after surgery. In the incomplete preservation group, these scores temporarily decreased (3 and 6 months after surgery), but such deterioration was not observed in the complete preservation group. Most of the 12 patients with potentially active erectile function before the operation recovered this function, and only one patient (7%) with PAN injury was still judged as inactive 12 months after surgery. CONCLUSION: The proportion of patients with sexual dysfunction after LTME is low. With the enhanced visibility of the laparoscope, inadvertent PAN injury was detected in a significant number of cases and associated with transient deterioration of sexual function.

Association of CTLA-4 gene A/G polymorphism in Japanese type 1 diabetic patients with younger age of onset and autoimmune thyroid disease.

OBJECTIVE: We studied the association between type 1 diabetes with autoimmune thyroid disease (AITD) and A/G allele polymorphism in exon 1 of the CTLA-4 gene in a Japanese population. RESEARCH DESIGN AND METHODS: We studied 74 Japanese type 1 diabetic patients with or without AITD and 107 normal subjects to identify the association between CTLA-4 polymorphism and type 1 diabetes using polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: The frequency of the CTLA-4 G allele differed significantly between the type 1 diabetic patients (61%) and the normal control subjects (48%) (P = 0.016). The difference in the CTLA-4 G allele became greater between patients with a younger age of onset of type 1 diabetes (age at onset <30 years) and the normal control subjects (64% and 48%, respectively). However, the frequency of the CTLA-4 G allele did not differ between type 1 diabetic patients with younger and older age of onset (64% vs. 57%). The G allele frequencies in the patients with younger-onset type 1 diabetes and AITD increased more than in the control patients (P = 0.025). These differences reflected a significant increase in the frequency of G/G genotype--that is, 54% in those with younger-onset type 1 diabetes and AITD, 39% in those without AITD, and 28% in control subjects. CONCLUSIONS: An association was detected between the CTLA-4 gene polymorphism and younger-onset type 1 diabetes with AITD. The G variant was suggested to be genetically linked to AITD-associated type 1 diabetes of younger onset in this apanese population. The defect in these patients presumably lies in a T-cell-mediated autoimmune mechanism.

Reduced host resistance and Th1 response to Cryptococcus neoformans in interleukin-18 deficient mice.

Using interleukin (IL)-18 deficient (IL-18(-/-)) mice, we examined the role of IL-18 in the host resistance and Th1 response against infection with Cryptococcus neoformans. Fungal clearance in the lung was reduced in IL-18(-/-) mice, although there was no significant change in the level of dissemination to the brain. The DTH response, as determined by footpad swelling, was also diminished in IL-18(-/-) mice compared to control wild-type (WT) mice. The levels of IL-12 and interferon (IFN)-gamma in the sera were significantly lower in IL-18(-/-) mice than in WT mice. Spleen cells from infected WT mice produced a high level of IFN-gamma upon stimulation with the microbe, while only a low level of IFN-gamma production was detected in spleen cells from infected IL-18(-/-) mice. Administration of IL-18 almost completely restored the reduced response in IL-18(-/-) mice, while IL-12 showed a marginal effect. These results demonstrated the important role of IL-18 in the resistance and Th1 response of mice to C. neoformans by potentiating the production of IFN-gamma.

Human brain disturbance by methylmercury poisoning, focusing on the long-term effect on brain weight.

The long-term effects of the initial methylmercury exposure in the Minamata area were examined, with focus on brain weight. Comparisons were made between the brain weights of methylmercury-contaminated persons in the Minamata area (cases) and those of Japanese who suffered sudden or accidental death without brain disease (controls). Since over thirty years have passed since the outbreak of Minamata disease, subjects aged 30 or over at death were included in the analysis. The total number of cases was 417 (273 males, 144 females) and that of controls was 2,934 (2,174 males, 760 females). The data suggest that the brain weights from Minamata cases were reduced by 80 to 200g as compared to the controls. These results may indicate that methylmercury exposure led to a decrease of nerve cells (single cell necrosis), so-called "thinning out", in the brain cortex.

Complexation of thiomalic acid with mercury (II) and lead (II) under physiological conditions.

The complex formation of thiomalic acid (H3L) with Hg(II) and Pb(II) was investigated under physiological conditions of 37 degrees C and 0.15 mol dm-3 NaCl by potentiometric titrations using glass electrodes. From the analysis of the emf data in the two systems by use of computer program MIQUV it was concluded that the species formed in the two systems are [HgH4L2], [HgH3L]-, [HgH2L2]2-, [HgHL2]3-, [HgHL], [HgL]-, [HgL2]4-, [Hg(OH)L]2-, [Hg(OH)L2]5-, [PbH2L2]2-, [PbH2L]+, [PbHL2]3-, [PbHL], [PbL]-, [Pb(OH)L]2-, and [Pb(OH)2L]3-. The hydrolytic reactions of Hg(II), data on which were used in the analysis of the above system, were also studied by separate potentiometric titrations. Measurements of 13C NMR spectra of [HgL2]4- and [PbL]- and [PbHL2]3- in D2O solutions suggested that the ligand coordinates with both the metal ions through the sulfhydryl group and one of the two carboxylate groups in such a way that the five-membered chelate ring is formed within the complexes.

[Clinical studies on SM-4300, a new intravenous human gamma-globulin].

With the recent development of new potential antibiotics, it has become easier to treat patients with common bacterial infections. However, we find it difficult to handle severe infections due to opportunistic pathogens, developed in the so-called immunocompromised patients. SM-4300 is a newly developed intravenous human gamma-globulin, which is said to be intact without conventional enzyme-treatment and sulfonization. SM-4300 is also free from large molecules of aggregated gamma-globulin. SM-4300 was administered in combination with antibiotics to 2 patients of severe respiratory infections, having refractory underlying diseases. Case No. 1 was a 65-year-old female with bronchopneumonia, who had been suffering from pulmonary fibrosis, chronic bronchitis, chronic congestive heart failure and tricuspid insufficiency for several years. During her hospitalization because of these diseases, she developed cough with slight sputum and exertional dyspnea accompanied by high body temperature of 38 degrees C on January 1983. Chest X-ray revealed infiltration in the right lung field which was compatible with bronchopneumonia. SM-4300 of 5 g was added intravenously on 5th day after 4 day-cefotiam treatment with no improvement. High body temperature subsided and laboratory data became normal around 3 days after single SM-4300 injection. Case No. 2 was a 68-year-old male patient of chronic bronchitis with chronic pulmonary emphysema and bronchial asthma. Around the end of May 1983, he complained of dyspnea on exertion and had mucopurulent sputum, more than 100 ml daily, from which Pseudomonas aeruginosa was cultured in large number. He was afebrile.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effectiveness of ceftizoxime on various infections in patients with underlying diseases].

Ceftizoxime (CZX), a parenteral cephalosporin derivative belonging to the so-called third generation cephalosporin is reported to have a broad antibacterial activity, particularly against Gram-negative aerobic bacilli and some anaerobes, such as Bacteroides fragilis and a good stability to beta-lactamases. Clinical study was performed on a total of 20 cases, 9 females (1 case had urinary tract infection 3 times) and 11 males, aged from 27 to 82 years. All patients had the underlying diseases. They were bronchial asthma in 3 cases, influenza in 1, chronic pulmonary emphysema in 1, pulmonary fibrosis in 1, chronic bronchitis with strongyloidiasis in 1, lung cancer in 3, esophagus cancer in 2, stomach cancer in 1, hepatoma with urolithiasis in 1, liver cirrhosis with diabetes mellitus in 1, alcoholism with strongyloidiasis in 1, cholelithiasis in 1 and congestive heart failure in 1, respectively. Clinical diagnoses for infections were 2-acute bronchitis, 2-exacerbation of chronic bronchitis, 2-broncho-pneumonia, 2-pneumonia including one suspected case, 1-obstructive pneumonia, 2-secondary pulmonary infection, 1-pulmonary infection, 3-urinary tract infection (UTI), 1-UTI with sepsis, 1-sepsis, 1-sepsis with purulent meningitis, 1-biliary tract infection and 1-infected bronchoesophageal fistula. CZX was given by intravenous drip infusion, at a dose of 1 to 2 g, twice daily for 3 to 15 days. Because of severity in infections and underlying diseases, some cases were treated either steroid, gamma-globulin preparations or other antibiotics in combination with CZX. Twelve out of 15 cases assessed clinically responded satisfactorily to the treatment and efficacy rate was 80.0%.(ABSTRACT TRUNCATED AT 250 WORDS)

[A study of victims of methylmercury poisoning outbreaks by age and sex in Minamata, Niigata and Iraqi outbreaks].

To investigate features of the incidence of methylmercury poisoning cases presumably caused by intake of polluted foods in Japan and Iraq, several populations exposed to polluted foods were analyzed by geography and/or occupation. Ratios of confirmed cases to the corresponding number by age and sex in the defined exposed population were calculated. The distribution of the ratios showed a unimodal age distribution for both males and females in the Japanese Minamata and Niigata population. On the contrary, in the Iraqi population, ratios distributed equally by age and sex groups, having no peaks. This difference between the two countries is probably due to the difference of ingestion by age and sex in fish and wheat, which was the primary source of methylmercury exposure.

[Influence of age and sex on threshold dose of mercury in Minamata disease as determined by hair mercury concentration].

The influence of age and sex on the threshold dose of mercury in Minamata disease was studied by dose-response analysis based on mercury concentrations in hair obtained mainly from adults living near the Agano River at the beginning of Niigata Minamata disease outbreak in 1965. The subjects were 174 male and 694 female inhabitants of polluted areas including 55 males and 66 females officially recognized as Minamata disease patients. Because of the large sex differences in numbers and age distributions, the data were analyzed separately for males and females. While revealing no sex difference in the threshold dose, hockey-stick regression analysis indicated an effect of age on threshold dose in females. Logistic regression analysis showed no interaction between age and hair mercury concentration. These results suggest that, in adults, neither sex nor age exert a considerable effect on the threshold dose of mercury in Minamata disease.

[A cross-sectional study of lipid peroxide levels (plasma TBA levels) in a mass health examination].

Differences in plasma thiobarbituric acid (TBA) levels were studied by sex and age in 1,178 adults (471 males and 707 females) participating in a mass health examination conducted in a town of Kumamoto Prefecture in 1989. The relationships between plasma TBA levels and obesity, the consumption of cigarettes, alcohol, and fish, and various indices for health status derived from the data of physiological examinations were analyzed in age-groups 40-59 and 60-79 for both sexes. The prevalence of abnormal physiological findings by plasma TBA levels were further investigated. The results were as follows; 1. The highest plasma TBA levels for males were observed in the group aged 40-49, with levels gradually decreasing with age thereafter. The plasma TBA levels for females increased with age and the highest levels were obtained at age 60-69. The plasma TBA levels for males were significantly higher than for females at aged 40-49. 2. Plasma TBA levels for both sexes increased with obesity and the amount of fish consumed. 3. Plasma TBA levels in all examined groups had significant and strong positive correlations with serum total cholesterol levels and atherogenic indices, and had significant positive correlations with serum calcium and gamma-GTP levels. 4. A stepwise multiple regression analysis showed that plasma TBA levels for males were associated with serum total cholesterol, gamma-GTP, fish consumption and serum HDL-cholesterol in that order. The levels for female were associated with serum total cholesterol, body mass index, serum HDL-cholesterol and serum calcium in that order. The relationship with serum HDL-cholesterol was a negative correlation. 5. Prevalence of abnormal values of serum total cholesterol, atherogenic index and body mass index were significantly higher in the high-plasma TBA level group than in the group with median-plasma TBA level. These results suggest that plasma TBA levels may be useful as an index of undesirable lipid metabolism. Further studies should be performed to establish the significance of the relation of plasma TBA levels to fish consumption.

Polymorphisms of interleukin (IL)-4 receptor alpha and signal transducer and activator of transcription-6 (Stat6) are associated with increased IL-4Ralpha-Stat6 signalling in lymphocytes and elevated serum IgE in patients with Graves' disease.

Activated interleukin (IL)-4Ralpha stimulates production of IgE through signal transducer and activator of transcription-6 (Stat6) activation in lymphocytes. Genetic studies have shown an association between polymorphisms in the genes encoding IL-4Ralpha and Stat6 and elevated serum IgE in patients with atopic disease. Some authors, including us, have reported an association of Graves' disease and elevated serum IgE. To analyse the relationship between IL-4Ralpha and Stat6 polymorphisms and elevated serum IgE in patients with Graves' disease, 169 patients with Graves' disease were studied. We investigated whether these polymorphisms affect IL-4Ralpha-Stat6 signalling in cultured human lymphocytes. A high frequency of both the Ile50 polymorphism in IL-4Ralpha and 13GT repeat variants of the Stat6 gene was observed in patients with Graves' disease and elevated serum IgE (Ile50 allele; P < 0.05, 13GT allele; P < 0.01 versus controls) but not in subjects with normal IgE. Cultured human lymphocytes with the Ile50 IL-4Ralpha polymorphism and the 13GT repeat variant of Stat6 showed increased IL-4 (and/or IL-13)-induced Stat6 activation (2.7-fold; P < 0.05 and 2.2-fold; P < 0.05, respectively). These findings suggest that polymorphisms in the IL-4Ralpha and Stat6 genes play an important role in elevation of serum IgE through increased Stat6 action in patients with Graves' disease.

CpG oligodeoxynucleotides promote the host protective response against infection with Cryptococcus neoformans through induction of interferon-gamma production by CD4+ T cells.

In the present study, we elucidated the effect of synthetic CpG-containing oligodeoxynucleotides (ODN) on pulmonary and disseminated infection caused by Cryptococcus neoformans. CDF-1 mice were inoculated intratracheally with a highly virulent strain of this pathogen, which resulted in massive bacterial growth in the lung, dissemination to the brain and death. Administration of CpG-ODN promoted the clearance of C. neoformans in the lungs, decreased their dissemination to brain and prolonged the survival of infected mice. These effects correlated well with the enhanced production of interleukin (IL)-12 and interferon (IFN)-gamma and attenuated secretion of IL-4 in bronchoalveolar lavage fluids (BALF) and promoted development of Th1 cells, as indicated by the increased production of IFN-gamma by paratracheal lymph node cells upon restimulation with cryptococcal antigens. The IFN-gamma synthesis in BALF was inhibited by depletion of CD8(+) and CD4(+) T cells on days 7 and 14 after infection, respectively, but not by depletion of NK and gammadelta T cells. Consistent with these data, intracellular expression of IFN-gamma was detected predominantly in CD8(+) and CD4(+) T cells in the lung on days 7 and 14, respectively. The protective effect of CpG-ODN, as shown by the prolonged survival, was completely and partially inhibited by depletion of CD4(+) or CD8(+) T cells, respectively, but not by depletion of other cells. Finally, TNF-alpha was markedly induced by CpG-ODN, and the protective effect of this agent was strongly inhibited by neutralizing anti-TNF-alpha MoAb. Our results indicate that CpG-ODN alters the Th1-Th2 cytokine balance and promotes host resistance against infection with C. neoformans.

Fine structure of unstained human chromosome fibres dried with no fixative as observed by X-ray contact microscopy.

X-ray contact microscopy was used to examine unstained human chromosomes dried without any fixative. This is the first report of the observation of single human chromosome fibres at high resolution without any modification(s) such as staining or fixation. The 'beads-on-a-string' structure was observed in stretched portions of chromosome fibres. The diameters of the thin filaments and small particles were 7-15 nm (mean +/- SD of 12.2 +/- 2.1 nm) and 16-69 nm (31.4 +/- 13.2 nm), respectively. These sizes correspond to those of fibres composed of nucleosomes (10-15 nm in diameter) and particle units (15-50 nm in diameter) called superbeads (unit structures composed of a multiple association of nucleosomes). These results are in good agreement with the current nucleosome and superbead model for chromosome fibre structure.

Ultraviolet radiation and health: from hazard identification to effective prevention.

The increased exposure to ultraviolet (UV) radiation due to ozone depletion is one of the most serious global health problems. The UV exposure is known to cause skin carcinoma, cataract and deteriorated immune function, but for countries like Japan, the magnitude of health effects of UV radiation is yet to be elucidated. The International Workshop on the Health Effects of Ultraviolet Radiation was held in Tokyo, Japan, on February 17-19, 1999, in attempts to visualize the size of this problem and to identify better solutions. Through this workshop, several lines of scientific evidence were provided, which clearly show that the risk of cataract and skin cancer among people living in Japan increases with the increasing level of sun exposure. We must seek, therefore, the extent to which the UV exposure of given intensity causes adverse health effects in Japanese population. Through the workshop, the importance of preventive measure was confirmed. The scientific basis of prevention is, of course, the knowledge of dose-response relationship and the current exposure status in Japanese population. It is hoped that the communications between researchers in Japan and other countries are strengthened through this workshop.

Profile of subjective complaints and activities of daily living among current patients with Minamata disease after 3 decades.

We surveyed 1144 current patients with Minamata disease (MD) aged 40 or over in the Minamata area and the same number of neighbor controls matched with age and sex by questionnaire interview with regard to subjective complaints and activities of daily living (ADL). From analysis of subjective complaints, it was found that MD patients had significantly higher rates of all complaints than controls (P < 0.05). Multivariate analysis showed that subjective complaints in controls were clearly separated into the following two categories: sensory disturbances and movement nerve disturbances, but all complaints in MD patients formed one cluster. Such variation seemed to be due to methylmercury exposure to the central nervous system. ADL analysis revealed that the difference in the ADL disability between MD patients and controls significantly increased with age (P < 0.05) and that ADL disability in MD patients was aggravated by aging.

Present mercury levels in red blood cells of nearby inhabitants about 30 years after the outbreak of Minamata disease.

Samples of red blood cells (RBCs) from 1178 inhabitants, consisting of 546 males and 795 females (over 40 years old), of a coastal town near Minamata City were analyzed for total mercury. The mercury concentrations in the RBCs showed lognormal distributions for both sexes with higher values in males than in females. The geometric mean of the mercury concentrations in the RBCs was 27.5 ng/g (ranging from 8.0 to 69.1 ng/g) for males and 20.4 ng/g (ranging from 7.0 to 63.7 ng/g) for females. The mercury concentrations in the RBCs decreased with advancing age. A significant regression between the geometric mean of the mercury concentrations in the RBCs and age was obtained for both sexes. The mercury concentrations in the RBCs from male inhabitants of the coastland area were significantly higher than those from male inhabitants of the inland area. In terms of occupation, the highest mercury concentrations were observed in the RBCs from fisherman. No significant difference in the present mercury concentrations in the RBCs was observed between the cases with Minamata disease and the controls.